Compositions and methods of treating liver disease

a technology applied in the field of compositions and methods of treating liver disease, can solve the problems that the occurrence of pnald is often recognized too, and achieve the effect of treating or reducing the occurrence of steatohepatitis disorder

Active Publication Date: 2019-10-17
CHILDRENS HOSPITAL MEDICAL CENT CINCINNATI
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Problems solved by technology

Because its progression is typically insidious and its long-term consequences are generally underappreciated, PNALD is often recognized too late, when liver injury is irreversible.

Method used

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  • Compositions and methods of treating liver disease
  • Compositions and methods of treating liver disease

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Repurposing OCA for PNALD Therapy

[0049]In this study, Applicant found that OCA and FGF19 inhibited ROS production caused by Intralipid exposure in HLO, leading to an improvement in survival rate of HLO. Moreover, the stiffness of OA treated HLO, measured by AFM, was decreased by FGF19 exposure. These results provide direct experimental evidence that OCA and FGF19 play a preventive role in the pathogenesis of PNALD organoid model and that the suppression of ROS production and fibrosis by FXR agonism is the likely mechanism of protection against PNALD. Our study thus highlighted the potential repurposing of OCA for the treatment of patients with PNALD.

[0050]Obeticholic acid treatment improved PNALD-like pathology of HLO

[0051]PNALD is an iatrogenic fatty liver disease which occurs frequently in infants provided with parental nutrition (PN) solutions employing a lipid emulsion (Intralipid) that provide life-sustaining calories in the setting of inadequate absorption of enteral nutrients...

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Abstract

Disclosed are methods of treating or reducing the occurrence of a steatohepatitis disorder. The disorder may include, for example, NASH, parenteral nutrition associated liver disease (PNALD), or genetic forms of liver disease. The method may comprise the step of administering a composition comprising obeticholic acid to an individual in need thereof.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to and benefit of U.S. Provisional Patent Application 62 / 471,371, filed Nov. 4, 2016, and 62 / 517,414, filed Jun. 9, 2016, the contents of each are incorporated by reference in their entirety for all purposes.BACKGROUND[0002]PNALD is the most devastating complication of long-term PN that occurs in the majority of children receiving PN (Kumar and Teckman, 2015; Orso et al., 2016; Zambrano et al., 2004). Because its progression is typically insidious and its long-term consequences are generally underappreciated, PNALD is often recognized too late, when liver injury is irreversible. It is histologically characterized by intrahepatic cholestasis but can progress to fibrosis and cirrhotic liver failure with continued exposure to PN. There are no established ameliorative strategies for PNALD and PNALD is the leading indication for liver transplantation in infants (El Kasmi et al., 2013).BRIEF SUMMARY[0003]Disclos...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/575A61P1/16A61K9/00
CPCA61K9/0029A61P1/16A61K31/575C12N5/0671C12N2501/119C12N2506/45G01N33/5088C12N2500/38C12N2501/727G01N2800/52A61K35/407A61K45/06C12N5/0696C12N15/01C12N5/0672C12N5/0697C12N2500/36G01N33/5008
Inventor TAKEBE, TAKANORIOUCHI, RIE
Owner CHILDRENS HOSPITAL MEDICAL CENT CINCINNATI
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